caa a22 4500 39759349X CHVBK 20180308164945.0 cr unu---uuuuu 161202e199603 xx s 000 0 eng 10.1093/jac/37.3.491 doi (NATIONALLICENCE)oxford-10.1093/jac/37.3.491 Comparison of the activity of fluoroquinolones against Mycobacterium avium in cell-free systems and a human monocyte in-vitro infection model [Elektronische Daten] [Hiroe Shiratsuchi, Michael R. Jacobs, Anthony J. Pearson, Nandagopal Venkataprasad, Gilles Klopman, Jerrold Ellner] Mycobacterium avium frequently causes disseminated infection in advanced AIDS. Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium activity in cell-free systems in vitro. Acidic conditions within macrophages and variable intracellular drug penetration and compartmentalization may, however, alter the susceptibility of M. avium to these antimicrobial agents in human tissues. We, therefore, tested the activities of 47 quinolones against M. avium in a human monocyte infection model using ciprofloxacin susceptible (MIC = 0.25 mg/L) and resistant (MIC = 4 mg/L) patient isolates. Monocytes from healthy subjects were infected with M. avium and cultured with or without antimicrobials for 8 days. Some quinolones had poor activity against M. avium in the monocyte culture system despite low MICs (≤0.25 mg/L); in contrast, some quinolones with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at 4 mg/L. Six quinolones synthesized based on structure-activity analysis were more active than ciprofloxacin. These data underscore the importance of evaluating drug activity of new antimicrobial agents against intracellular pathogens in a macrophage model as well as in cell-free systems. © 1996 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Shiratsuchi Hiroe Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Jacobs Michael R. Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Pearson Anthony J. Chemistry Department, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Venkataprasad Nandagopal Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Klopman Gilles Chemistry Department, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Ellner Jerrold Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 37/3(1996-03), 491-500 0305-7453 37:3<491 1996 37 jac https://doi.org/10.1093/jac/37.3.491 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.3.491 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shiratsuchi Hiroe Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 700 1- Jacobs Michael R. Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 700 1- Pearson Anthony J. Chemistry Department, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 700 1- Venkataprasad Nandagopal Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 700 1- Klopman Gilles Chemistry Department, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 700 1- Ellner Jerrold Department of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37/3(1996-03), 491-500 0305-7453 37:3<491 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford